Molecular Biomarkers in Traumatic Brain Injury: Diagnostic, Prognostic, and Therapeutic Perspective

Authors

Febi Jian Setiasari , Shaffani Mahasuary Putri , Baiq Sagitta Puspasari , Muhammad Fadani Ilham

DOI:

10.29303/jbt.v25i4.10237

Published:

2025-10-01

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Abstract

Traumatic Brain Injury (TBI) remains a major global health problem due to its high morbidity and mortality rates. TBI can lead to cognitive and emotional impairments, and even increase the risk of neurodegenerative diseases such as Alzheimer's and Parkinson's. This review was compiled by searching literature discussing the role of molecular biomarkers in TBI, both from diagnostic and prognostic perspectives, as well as their therapeutic potential. The article search was conducted via PubMed, ScienceDirect, and Google Scholar using relevant keywords. The findings showed that with the increasing number of TBI cases, the limitations of CT scans and the Glasgow Coma Scale (GCS) in assessing subtle brain damage have spurred interest in molecular biomarkers. Biomarkers such as GFAP, S100B, tau protein, UCH-L1, and NF-L have been shown to detect biological changes not visible on routine imaging. GFAP emerges as the most promising candidate due to its high sensitivity and specificity in assessing injury severity. Thus, molecular biomarkers have the potential to improve diagnostic accuracy, predict prognosis, and support more effective rehabilitation strategies. The conclusion is that TBI is a global health problem with serious long-term impacts. Molecular biomarkers offer a great opportunity to complement conventional diagnostic methods. Although challenges remain in validation, standardization, and clinical application, further research can pave the way for the use of biomarkers as diagnostic and prognostic tools, as well as a basis for more personalized therapy in TBI patients.

Keywords:

Biomarkers, molecular, traumatic brain injury.

References

Agoston, D. V., & Helmy, A. (2023). Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside. In International Journal of Molecular Sciences (Vol. 24, Issue 22). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/ijms242216267

Akhyar, R. B. F., Rosyidi, R. M., & Priyanto, B. (2023). TINJAUAN PUSTAKA: DIAGNOSIS DAN TATALAKSANA CEDERA OTAK TRAUMATIK. In Jurnal Ilmu Kedokteran dan Kesehatan (Vol. 10, Issue 12). http://ejurnalmalahayati.ac.id/index.php/kesehatan

Behzadi, F., Luy, D. D., Schaible, P. A., Zywiciel, J. F., Puccio, A. M., & Germanwala, A. V. (2024). A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury. Clinical Neurology and Neurosurgery, 242, 108312. https://doi.org/10.1016/j.clineuro.2024.108312

Brandl, S., & Reindl, M. (2023). Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models. In International Journal of Molecular Sciences (Vol. 24, Issue 16). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/ijms241612699

Brazinova, A., Rehorcikova, V., Taylor, M. S., Buckova, V., Majdan, M., Psota, M., Peeters, W., Feigin, V., Theadom, A., Holkovic, L., & Synnot, A. (2021). Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review. In Journal of Neurotrauma (Vol. 38, Issue 10, pp. 1411–1440). Mary Ann Liebert Inc. https://doi.org/10.1089/neu.2015.4126

Butkova, T. V., Malsagova, K. A., Nakhod, V. I., Petrovskiy, D. V., Izotov, A. A., Balakin, E. I., Yurku, K. A., Umnikov, A. S., Pustovoyt, V. I., & Kaysheva, A. L. (2024). Candidate Molecular Biomarkers of Traumatic Brain Injury: A Systematic Review. In Biomolecules (Vol. 14, Issue 10). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/biom14101283

Chamoun, R., Suki, D., Gopinath, S. P., Goodman, J. C., & Robertson, C. (2010). Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury: Clinical article. Journal of Neurosurgery, 113(3), 564–570. https://doi.org/10.3171/2009.12.JNS09689

Cho, M. J., & Jang, S. H. (2021). Relationship between post-traumatic amnesia and white matter integrity in traumatic brain injury using tract-based spatial statistics. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-86439-0

Dadas, A., Washington, J., Diaz-Arrastia, R., & Janigro, D. (2018). Biomarkers in traumatic brain injury (TBI): A review. In Neuropsychiatric Disease and Treatment (Vol. 14, pp. 2989–3000). Dove Medical Press Ltd. https://doi.org/10.2147/NDT.S125620

Diaz-Arrastia, R., Wang, K. K. W., Papa, L., Sorani, M. D., Yue, J. K., Puccio, A. M., McMahon, P. J., Inoue, T., Yuh, E. L., Lingsma, H. F., Maas, A. I. R., Valadka, A. B., Okonkwo, D. O., Manley, G. T., Casey, I. S. S., Cheong, M., Cooper, S. R., Dams-O’Connor, K., Gordon, W. A., … Vassar, M. J. (2014). Acute biomarkers of traumatic brain injury: Relationship between plasma levels of ubiquitin C-terminal hydrolase-l1 and glial fibrillary acidic protein. Journal of Neurotrauma, 31(1), 19–25. https://doi.org/10.1089/neu.2013.3040

Gao, T. L., Yuan, X. T., Yang, D., Dai, H. L., Wang, W. J., Peng, X., Shao, H. J., Jin, Z. F., & Fu, Z. J. (2012). Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury. Journal of Trauma and Acute Care Surgery, 72(3), 643–649. https://doi.org/10.1097/TA.0b013e31823c54a6

Ghaith, H. S., Nawar, A. A., Gabra, M. D., Abdelrahman, M. E., Nafady, M. H., Bahbah, E. I., Ebada, M. A., Ashraf, G. M., Negida, A., & Barreto, G. E. (2022). A Literature Review of Traumatic Brain Injury Biomarkers. In Molecular Neurobiology (Vol. 59, Issue 7, pp. 4141–4158). Springer. https://doi.org/10.1007/s12035-022-02822-6

Gutierre, M. U., Telles, J. P. M., Welling, L. C., Rabelo, N. N., Teixeira, M. J., & Figueiredo, E. G. (2021). Biomarkers for traumatic brain injury: a short review. In Neurosurgical Review (Vol. 44, Issue 4, pp. 2091–2097). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/s10143-020-01421-0

Hall, E. D., Vaishnav, R. A., & Mustafa, A. G. (2010). Antioxidant Therapies for Traumatic Brain Injury.

Hossain, I., Marklund, N., Czeiter, E., Hutchinson, P., & Buki, A. (2023). Blood biomarkers for traumatic brain injury: A narrative review of current evidence. Brain & Spine, 4, 102735. https://doi.org/10.1016/j.bas.2023.102735

Johnson, N. H., Hadad, R., Taylor, R. R., Pilar, J. R., Salazar, O., Llompart-Pou, J. A., Dietrich, W. D., Keane, R. W., Pérez-Bárcena, J., & Vaccari, J. P. de R. (2022). Inflammatory Biomarkers of Traumatic Brain Injury. Pharmaceuticals, 15(6). https://doi.org/10.3390/ph15060660

Johnson, V. E., Stewart, W., & Smith, D. H. (2013). Axonal pathology in traumatic brain injury. In Experimental Neurology (Vol. 246, pp. 35–43). https://doi.org/10.1016/j.expneurol.2012.01.013

Juwita, Hidayaturrahmi, Adista, M. A., & Khairunnisa. (2024). Biomarker Prognostik pada Cedera Otak Traumatik: Manakah yang Terbaik? 5.

Krausz, A. D., Korley, F. K., & Burns, M. A. (2021). The current state of traumatic brain injury biomarker measurement methods. Biosensors, 11(9). https://doi.org/10.3390/bios11090319

Kuhle, J., Barro, C., Andreasson, U., Derfuss, T., Lindberg, R., Sandelius, Å., Liman, V., Norgren, N., Blennow, K., & Zetterberg, H. (2016). Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clinical Chemistry and Laboratory Medicine, 54(10), 1655–1661. https://doi.org/10.1515/cclm-2015-1195

Lipsky, R. H., Witkin, J. M., Shafique, H., Smith, J. L., Cerne, R., & Marini, A. M. (2024). Traumatic brain injury: molecular biomarkers, genetics, secondary consequences, and medical management. In Frontiers in Neuroscience (Vol. 18). Frontiers Media SA. https://doi.org/10.3389/fnins.2024.1446076

Lu, B., Nagappan, G., Guan, X., Nathan, P. J., & Wren, P. (2013). BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. In Nature Reviews Neuroscience (Vol. 14, Issue 6, pp. 401–416). https://doi.org/10.1038/nrn3505

Maas, A. I. R., Menon, D. K., Manley, G. T., Abrams, M., Åkerlund, C., Andelic, N., Aries, M., Bashford, T., Bell, M. J., Bodien, Y. G., Brett, B. L., Büki, A., Chesnut, R. M., Citerio, G., Clark, D., Clasby, B., Cooper, D. J., Czeiter, E., Czosnyka, M., … Zumbo, F. (2022). Traumatic brain injury: progress and challenges in prevention, clinical care, and research. In The Lancet Neurology (Vol. 21, Issue 11, pp. 1004–1060). Elsevier Ltd. https://doi.org/10.1016/S1474-4422(22)00309-X

Magnusson, B. M., & Koskinen, L. O. D. (2024). Classification and Characterization of Traumatic Brain Injuries in the Northern Region of Sweden. Journal of Clinical Medicine, 13(1). https://doi.org/10.3390/jcm13010008

Mahley, R. W. (1988). Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology. www.sciencemag.org

Mcconeghy, K. W., Hatton, J., Hughes, L., & Cook, A. M. (2012). A Review of Neuroprotection Pharmacology and Therapies in Patients with Acute Traumatic Brain Injury.

McFadyen, C. A., Zeiler, F. A., Newcombe, V., Synnot, A., Steyerberg, E., Gruen, R. L., Rosand, J., Palotie, A., Maas, A. I. R., & Menon, D. K. (2021). Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury: A Living Systematic Review and Meta-Analysis. In Journal of Neurotrauma (Vol. 38, Issue 8, pp. 1124–1136). Mary Ann Liebert Inc. https://doi.org/10.1089/neu.2018.6052

Mena, J. H., Sanchez, A. I., Rubiano, A. M., Peitzman, A. B., Sperry, J. L., Gutierrez, M. I., & Puyana, J. C. (2011). Effect of the modified glasgow coma scale score criteria for mild traumatic brain injury on mortality prediction: Comparing classic and modified glasgow coma scale score model scores of 13. Journal of Trauma - Injury, Infection and Critical Care, 71(5), 1185–1193. https://doi.org/10.1097/TA.0b013e31823321f8

Michetti, F., D’Ambrosi, N., Toesca, A., Puglisi, M. A., Serrano, A., Marchese, E., Corvino, V., & Geloso, M. C. (2019). The S100B story: from biomarker to active factor in neural injury. In Journal of Neurochemistry (Vol. 148, Issue 2, pp. 168–187). Blackwell Publishing Ltd. https://doi.org/10.1111/jnc.14574

Mondello, S., Papa, L., Buki, A., Bullock, M. R., Czeiter, E., Tortella, F. C., Wang, K. K., & Hayes, R. L. (2011). Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: A case control study. Critical Care, 15(3). https://doi.org/10.1186/cc10286

Mondello, S., Shear, D. A., Bramlett, H. M., Dixon, C. E., Schmid, K. E., Dietrich, W. D., Wang, K. K. W., Hayes, R. L., Glushakova, O., Catania, M., Richieri, S. P., Povlishock, J. T., Tortella, F. C., & Kochanek, P. M. (2016). Insight into Pre-Clinical Models of Traumatic Brain Injury Using Circulating Brain Damage Biomarkers: Operation Brain Trauma Therapy. Journal of Neurotrauma, 33(6), 595–605. https://doi.org/10.1089/neu.2015.4132

Mondello, S., Sorinola, A., Czeiter, E., Vámos, Z., Amrein, K., Synnot, A., Donoghue, E., Sándor, J., Wang, K. K. W., Diaz-Arrastia, R., Steyerberg, E. W., Menon, D. K., Maas, A. I. R., & Buki, A. (2021). Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis. In Journal of Neurotrauma (Vol. 38, Issue 8, pp. 1086–1106). Mary Ann Liebert Inc. https://doi.org/10.1089/neu.2017.5182

Myrga, J. M., Juengst, S. B., Failla, M. D., Conley, Y. P., Arenth, P. M., Grace, A. A., & Wagner, A. K. (2016). COMT and ANKK1 Genetics Interact with Depression to Influence Behavior Following Severe TBI: An Initial Assessment. Neurorehabilitation and Neural Repair, 30(10), 920–930. https://doi.org/10.1177/1545968316648409

National Academies of Sciences, Engineering, and Medicine. (2019). Traumatic brain injury: A roadmap for accelerating progress. Washington, DC: National Academies Press. https://doi.org/10.17226/25394

Ng, S. Y., & Lee, A. Y. W. (2019). Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. In Frontiers in Cellular Neuroscience (Vol. 13). Frontiers Media S.A. https://doi.org/10.3389/fncel.2019.00528

Osthoff, M., Katan, M., Fluri, F., Schuetz, P., Bingisser, R., Kappos, L., Steck, A. J., Engelter, S. T., Mueller, B., Christ-Crain, M., & Trendelenburg, M. (2011). Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS ONE, 6(6). https://doi.org/10.1371/journal.pone.0021338

Papa, L., Ramia, M. M., Kelly, J. M., Burks, S. S., Pawlowicz, A., & Berger, R. P. (2013). Systematic review of clinical research on biomarkers for pediatric traumatic brain injury. In Journal of Neurotrauma (Vol. 30, Issue 5, pp. 324–338). https://doi.org/10.1089/neu.2012.2545

Raghupathi, R. (2004). Cell Death Mechanisms Following Traumatic Brain Injury.

Ramzi, A., & Hunaifi, I. (2024). Diagnosis and Management of Post Traumatic Epilepsy. Jurnal Biologi Tropis, 24(4), 403–412. https://doi.org/10.29303/jbt.v24i4.7667

Semple, B. D., Kossmann, T., & Morganti-Kossmann, M. C. (2010). Role of chemokines in CNS health and pathology: A focus on the CCL2/CCR2 and CXCL8/CXCR2 networks. In Journal of Cerebral Blood Flow and Metabolism (Vol. 30, Issue 3, pp. 459–473). https://doi.org/10.1038/jcbfm.2009.240

Shahim, P., Gren, M., Liman, V., Andreasson, U., Norgren, N., Tegner, Y., Mattsson, N., Andreasen, N., Öst, M., Zetterberg, H., Nellgård, B., & Blennow, K. (2016). Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Scientific Reports, 6. https://doi.org/10.1038/srep36791

Shahim, P., Linemann, T., Inekci, D., Karsdal, M. A., Blennow, K., Tegner, Y., Zetterberg, H., & Henriksen, K. (2016). Serum Tau Fragments Predict Return to Play in Concussed Professional Ice Hockey Players. Journal of Neurotrauma, 33(22), 1995–1999. https://doi.org/10.1089/neu.2014.3741

Shenton, M. E., Hamoda, H. M., Schneiderman, J. S., Bouix, S., Pasternak, O., Rathi, Y., Vu, M. A., Purohit, M. P., Helmer, K., Koerte, I., Lin, A. P., Westin, C. F., Kikinis, R., Kubicki, M., Stern, R. A., & Zafonte, R. (2012). A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. In Brain Imaging and Behavior (Vol. 6, Issue 2, pp. 137–192). Springer Science and Business Media, LLC. https://doi.org/10.1007/s11682-012-9156-5

Shlosberg, D., Benifla, M., Kaufer, D., & Friedman, A. (2010). Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. In Nature Reviews Neurology (Vol. 6, Issue 7, pp. 393–403). https://doi.org/10.1038/nrneurol.2010.74

Simon, D. W., McGeachy, M. J., Baylr, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017). The far-reaching scope of neuroinflammation after traumatic brain injury. In Nature Reviews Neurology (Vol. 13, Issue 3, pp. 171–191). Nature Publishing Group. https://doi.org/10.1038/nrneurol.2017.13

Slavoaca, D., Muresanu, D., Birle, C., Rosu, O. V., Chirila, I., Dobra, I., Jemna, N., Strilciuc, S., & Vos, P. (2020). Biomarkers in traumatic brain injury: new concepts. In Neurological Sciences (Vol. 41, Issue 8, pp. 2033–2044). Springer-Verlag Italia s.r.l. https://doi.org/10.1007/s10072-019-04238-y

Stępniewska, E., Kałas, M., Świderska, J., & Siemiński, M. (2024). mTBI Biological Biomarkers as Predictors of Postconcussion Syndrome—Review. In Brain Sciences (Vol. 14, Issue 5). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/brainsci14050513

Tajik, M., & Noseworthy, M. D. (2022). A review of molecular and genetic factors for determining mild traumatic brain injury severity and recovery. Brain Disorders, 8, 100058. https://doi.org/10.1016/j.dscb.2022.100058

Tenovuo, O., Diaz-Arrastia, R., Goldstein, L. E., Sharp, D. J., van der Naalt, J., & Zasler, N. D. (2021). Assessing the severity of traumatic brain injury—time for a change? In Journal of Clinical Medicine (Vol. 10, Issue 1, pp. 1–12). MDPI. https://doi.org/10.3390/jcm10010148

Thelin, E. P., Zeiler, F. A., Ercole, A., Mondello, S., Büki, A., Bellander, B. M., Helmy, A., Menon, D. K., & Nelson, D. W. (2017). Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review. In Frontiers in Neurology (Vol. 8, Issue JUL). Frontiers Media S.A. https://doi.org/10.3389/fneur.2017.00300

Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011). Apolipoprotein E in Alzheimer’s disease and other neurological disorders. In The Lancet Neurology (Vol. 10, Issue 3, pp. 241–252). https://doi.org/10.1016/S1474-4422(10)70325-2

Werner, C., & Engelhard, K. (2007). Pathophysiology of traumatic brain injury. In British Journal of Anaesthesia (Vol. 99, Issue 1, pp. 4–9). Oxford University Press. https://doi.org/10.1093/bja/aem131

Woodcock, T., & Morganti-Kossmann, M. C. (2013). The role of markers of inflammation in traumatic brain injury. Frontiers in Neurology, 4 MAR. https://doi.org/10.3389/fneur.2013.00018

Xiong, Y., Mahmood, A., & Chopp, M. (2013). Animal models of traumatic brain injury. In Nature Reviews Neuroscience (Vol. 14, Issue 2, pp. 128–142). https://doi.org/10.1038/nrn3407

Yip, P. K., Carrillo-Jimenez, A., King, P., Vilalta, A., Nomura, K., Chau, C. C., Egerton, A. M. S., Liu, Z. H., Shetty, A. J., Tremoleda, J. L., Davies, M., Deierborg, T., Priestley, J. V., Brown, G. C., Michael-Titus, A. T., Venero, J. L., & Burguillos, M. A. (2017). Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration. Scientific Reports, 7. https://doi.org/10.1038/srep41689

Yiu, G., & He, Z. (2006). Glial inhibition of CNS axon regeneration. In Nature Reviews Neuroscience (Vol. 7, Issue 8, pp. 617–627). https://doi.org/10.1038/nrn1956

Zetterberg, H., & Blennow, K. (2016). Fluid biomarkers for mild traumatic brain injury and related conditions. In Nature Reviews Neurology (Vol. 12, Issue 10, pp. 563–574). Nature Publishing Group. https://doi.org/10.1038/nrneurol.2016.127

Author Biographies

Febi Jian Setiasari, University Of Mataram

Author Origin : Indonesia

Shaffani Mahasuary Putri, Universitas Mataram

Author Origin : Indonesia

Baiq Sagitta Puspasari, Universitas Mataram

Author Origin : Indonesia

Muhammad Fadani Ilham, Universitas Mataram

Author Origin : Indonesia

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How to Cite

Setiasari, F. J., Putri, S. M., Puspasari, B. S., & Ilham, M. F. (2025). Molecular Biomarkers in Traumatic Brain Injury: Diagnostic, Prognostic, and Therapeutic Perspective. Jurnal Biologi Tropis, 25(4), 4997–5009. https://doi.org/10.29303/jbt.v25i4.10237

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